A biotech has developed an autologous CAR-T construct with potential application in oncology indication X. The construct
Question:
A biotech has developed an autologous CAR-T construct with potential application in oncology indication X. The construct shows favorable pre-clinical data and the product team is approaching a Request For Development (RFD) decision to proceed to first-in-human studies. This asset utilizes an established CD19 binder with proven safety and efficacy. The biotech has extensive experience with this binder. In addition, this asset incorporates novel enhancements that could improve product efficacy. The product team believes that this asset could bring patient benefit in a 3L setting and in a 2L setting.
The team has developed two potential clinical development plans (CDP) for this asset:
A) an approach using a single-arm design for the pivotal study in 3L followed by a confirmatory randomized controlled trial in the 2L setting and
B) an approach using a randomized controlled trial for the pivotal study in 3L followed by a randomized controlled trial in a 2L setting.
Approach A
Run a small single-arm Ph1 study, primarily to assess product safety but also seek an early signal on cell expansion. This study would take approximately 12 months to execute and would cost $20M. Upon successful completion of the Ph1 study, the team would initiate a pivotal study in a 3L setting. This study would be a single-arm efficacy study with a primary endpoint of PFS. This study would last approximately 24 months and cost approximately $60M. Registration would cost $10M.
Upon successful registration in 3L, the team would initiate a pivotal randomized controlled trial in a 2L setting. This study would last 36 months and cost $120M, followed by additional registration fees of
$10M. This study would also serve as a confirmatory trial for the 3L indication.
Launching in 2027, the total commercial value of the 3L indication would be $1700M. Launching in 2031, the commercial value of the 2L indication would be $2200M
Approach B
Run a small single-arm Ph1 study as in approach A. Upon successful completion of the Ph1 study, initiate a pivotal study in a 3L setting. This study would be a randomized controlled trial with a primary endpoint of PFS. This study would last approximately 36 months and cost approximately $120M. Registration would cost $10M.
Upon successful registration in 3L, the team would initiate a 2L study as in approach A.
Launching in 2028, the total commercial value of the 3L indication would be $1500M. Launching in 2032, the commercial value of the 2L indication is $2200M
Data for probability
Industry-wide PTRS benchmarks: Ph1 = 70%, Pivotal= 30%, Registration = 95%
Several CAR-T products have been registered using single-arm studies followed by confirmatory trials. However, the regulatory function has advised the product team that regulatory agencies are increasingly requesting randomized controlled trials prior to registration.
Questions
Perform a financial analysis on the two development approaches, including expected net present value (eNPV), expected development cost (eCost), and Productivity Index(eNPV/eCost).
Identify strategic or qualitative factors that influence your recommendation.
Where information is not available, please clearly state your assumptions.
Recommend a development approach for this asset. Please identify the key trade-offs in choosing one approach over the other.
Assume the commercial value figure is the net present value of all commercial cashflows, including sales, COGS, selling & marketing expenses, and royalties
Auditing and Assurance services an integrated approach
ISBN: 978-0132575959
14th Edition
Authors: Alvin a. arens, Randal j. elder, Mark s. Beasley